Rest–activity rhythm as a clinical biomarker: what are the next steps?
Authors: Leandro C Brito, Saurabh S Thosar
Journal: The Lancet Healthy Longevity (2023)

The endogenous circadian system drives physiological changes in accordance with periodic environmental changes, enabling humans to anticipate and adapt to daily changes—such as in temperature, feeding or fasting, and activity–rest cycles.1Golombek DA Rosenstein RE Physiology of circadian entrainment.Physiol Rev. 2010; 90: 1063-1102Crossref PubMed Scopus (710) Google Scholar There is an association between a disrupted endogenous circadian system and the development of some endocrine, cardiovascular, and neurological diseases.2Fishbein AB Knutson KL Zee PC Circadian disruption and human health.J Clin Invest. 2021; 131e148286 Crossref PubMed Scopus (40) Google Scholar Regular physical activity at sufficient intensity is recommended for its inverse association with reduced risk of chronic diseases and mortality.3Lear SA Hu W Rangarajan S et al.The effect of physical activity on mortality and cardiovascular disease in 130 000 people from 17 high-income, middle-income, and low-income countries: the PURE study.Lancet. 2017; 390: 2643-2654Summary Full Text Full Text PDF PubMed Scopus (653) Google Scholar, 4Stensvold D Viken H Steinshamn SL et al.Effect of exercise training for five years on all cause mortality in older adults-the Generation 100 study: randomised controlled trial.BMJ. 2020; 371m3485 PubMed Google Scholar A review of small, single-centre studies in controlled populations showed that managing the timing of structured exercise training programmes can affect glucose homoeostasis and cardiovascular system control (eg, blood pressure and heart rate).5Brito LC Marin TC Azevêdo L Rosa-Silva JM Shea SA Thosar SS Chronobiology of exercise: evaluating the best time to exercise for greater cardiovascular and metabolic benefits.Compr Physiol. 2022; 12: 3621-3639Crossref PubMed Scopus (2) Google Scholar Not only does the timing of structured exercise matter, but the timing of physical activity might also be important for optimal health maintenance and chronic disease prevention.6Feng H Yang L Liang YY et al.Associations of timing of physical activity with all-cause and cause-specific mortality in a prospective cohort study.Nat Commun. 2023; 14: 930Crossref PubMed Scopus (1) Google Scholar However, the association between rest–activity rhythm amplitude throughout the day and health outcomes remains unclear. In The Lancet Healthy Longevity, Hongliang Feng and colleagues7Feng H Yang L Ai S et al.Association between accelerometer-measured amplitude of rest–activity rhythm and future health risk: a prospective cohort study of the UK Biobank.Lancet Healthy Longev. 2023; 4: e200-e210Summary Full Text Full Text PDF Scopus (1) Google Scholar examine the associations between accelerometer-measured rest–activity rhythm amplitude and health risk in the general population. The authors conducted a retrospective analysis of 92 614 individuals with valid wrist-worn accelerometer data from the UK Biobank dataset, followed-up for an median of 6·4 years (IQR 5·8–6·9), and found that decreased rest–activity rhythm amplitude was associated with poor health outcomes and might constitute an important modifiable risk factor. Additionally, low rest–activity rhythm and moderate-to-vigorous physical activity amplitude had a stronger association with incidence disease and disease-specific mortality than other well documented rest–activity parameters (ie, sleep quality and other physical activity indicators), and the associations were robust and not modified by age or sex. Rest–activity rhythm amplitude is easy to measure objectively and could become a promising tool to identify individuals at risk of adverse health outcomes in public health and clinical practice. Ascoli-Israel and colleagues8Ancoli-Israel S Cole R Alessi C Chambers M Moorcroft W Pollak CP The role of actigraphy in the study of sleep and circadian rhythms.Sleep. 2003; 26: 342-392Crossref PubMed Scopus (1978) Google Scholar have previously used relative amplitude to calculate rest–activity rhythm and suggested that rest–activity rhythm amplitude might help to minimise the misinterpretation of findings due to disturbances caused by poor sleep, reinforcing the robustness of this indicator. Feng and colleagues7Feng H Yang L Ai S et al.Association between accelerometer-measured amplitude of rest–activity rhythm and future health risk: a prospective cohort study of the UK Biobank.Lancet Healthy Longev. 2023; 4: e200-e210Summary Full Text Full Text PDF Scopus (1) Google Scholar provided an important example of this association: an individual with sleep disturbances but a high level of daytime physical activity would still have a high rest–activity rhythm amplitude. Even though the potential of physical activity to mitigate the harmful effects of poor sleep is by no means an established fact, this finding is in accordance with a previous cohort in which associations between cardiometabolic diseases and sleep loss and poor sleep quality occurred mainly in individuals with low physical activity levels.9Huang BH Duncan MJ Cistulli PA Nassar N Hamer M Stamatakis E Sleep and physical activity in relation to all-cause, cardiovascular disease and cancer mortality risk.Br J Sports Med. 2022; 56: 718-724Crossref PubMed Scopus (47) Google Scholar Despite its potential for widespread use and its importance for clinical practice and public health, the development of rest–activity rhythm amplitude as a clinical biomarker is still in the early stages. Among other limitations, the observational nature of the retrospective analysis does not allow cause–effect conclusions to be drawn; randomised clinical trials will be needed to investigate the longitudinal effects of rest–activity rhythm amplitude on health outcomes. Low diversity in the individuals in the study also limits the generalisability of the findings;7Feng H Yang L Ai S et al.Association between accelerometer-measured amplitude of rest–activity rhythm and future health risk: a prospective cohort study of the UK Biobank.Lancet Healthy Longev. 2023; 4: e200-e210Summary Full Text Full Text PDF Scopus (1) Google Scholar thus, future studies should ensure that data is collected in low-income and middle-income countries where opportunities for structured exercise and built environments conducive to physical activity might be scarcer than in high-income countries. Notwithstanding the limitations, including those noted by the authors, rest–activity rhythm amplitude has immense potential for future research, which is essential to establish the clinical meaning and relevance of this biomarker. We declare no competing interests. Association between accelerometer-measured amplitude of rest–activity rhythm and future health risk: a prospective cohort study of the UK BiobankOur results suggest that low rest–activity rhythm amplitude might contribute to major health outcomes and provide further evidence to promote risk-modifying strategies associated with rest–activity rhythm to improve health and longevity. Full-Text PDF Open Access